IL305077A - A quinazoline compound for inducing degradation of the G12D mutant cras protein - Google Patents
A quinazoline compound for inducing degradation of the G12D mutant cras proteinInfo
- Publication number
- IL305077A IL305077A IL305077A IL30507723A IL305077A IL 305077 A IL305077 A IL 305077A IL 305077 A IL305077 A IL 305077A IL 30507723 A IL30507723 A IL 30507723A IL 305077 A IL305077 A IL 305077A
- Authority
- IL
- Israel
- Prior art keywords
- methyl
- phenyl
- hydroxy
- oxy
- compound
- Prior art date
Links
- -1 Quinazoline compound Chemical class 0.000 title claims description 249
- 230000015556 catabolic process Effects 0.000 title description 19
- 238000006731 degradation reaction Methods 0.000 title description 19
- 230000001939 inductive effect Effects 0.000 title description 10
- 101150105104 Kras gene Proteins 0.000 title description 5
- 150000001875 compounds Chemical class 0.000 claims description 579
- 150000003839 salts Chemical class 0.000 claims description 258
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 209
- 238000004519 manufacturing process Methods 0.000 claims description 153
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 130
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 127
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 110
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 68
- 206010061902 Pancreatic neoplasm Diseases 0.000 claims description 66
- 208000015486 malignant pancreatic neoplasm Diseases 0.000 claims description 66
- 201000002528 pancreatic cancer Diseases 0.000 claims description 66
- 208000008443 pancreatic carcinoma Diseases 0.000 claims description 66
- 229920006395 saturated elastomer Polymers 0.000 claims description 64
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 61
- 229910052760 oxygen Inorganic materials 0.000 claims description 48
- 229910052731 fluorine Inorganic materials 0.000 claims description 40
- 229910052717 sulfur Inorganic materials 0.000 claims description 39
- 229910052757 nitrogen Inorganic materials 0.000 claims description 38
- 125000000623 heterocyclic group Chemical group 0.000 claims description 35
- 125000003386 piperidinyl group Chemical group 0.000 claims description 33
- 125000001412 tetrahydropyranyl group Chemical group 0.000 claims description 33
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 32
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 30
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 30
- 125000003566 oxetanyl group Chemical group 0.000 claims description 30
- 239000001301 oxygen Substances 0.000 claims description 30
- 239000008194 pharmaceutical composition Substances 0.000 claims description 30
- 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 30
- 239000011593 sulfur Substances 0.000 claims description 30
- 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 30
- 125000005842 heteroatom Chemical group 0.000 claims description 29
- 229910052736 halogen Inorganic materials 0.000 claims description 28
- 150000002367 halogens Chemical class 0.000 claims description 28
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 27
- 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 26
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 26
- 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 24
- 229910052739 hydrogen Inorganic materials 0.000 claims description 23
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 22
- 229910052801 chlorine Inorganic materials 0.000 claims description 21
- 125000006001 difluoroethyl group Chemical group 0.000 claims description 21
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 20
- 125000002947 alkylene group Chemical group 0.000 claims description 19
- 125000001072 heteroaryl group Chemical group 0.000 claims description 19
- 229910052799 carbon Inorganic materials 0.000 claims description 17
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 17
- 125000004076 pyridyl group Chemical group 0.000 claims description 17
- 125000002757 morpholinyl group Chemical group 0.000 claims description 14
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 14
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 13
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 13
- 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 12
- 229910052721 tungsten Inorganic materials 0.000 claims description 12
- 238000011282 treatment Methods 0.000 claims description 10
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 10
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- AAOVKJBEBIDNHE-UHFFFAOYSA-N diazepam Chemical compound N=1CC(=O)N(C)C2=CC=C(Cl)C=C2C=1C1=CC=CC=C1 AAOVKJBEBIDNHE-UHFFFAOYSA-N 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 3
- 125000001207 fluorophenyl group Chemical group 0.000 claims 1
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- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 157
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- 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
- 230000006103 sulfonylation Effects 0.000 description 1
- 238000005694 sulfonylation reaction Methods 0.000 description 1
- 239000004094 surface-active agent Substances 0.000 description 1
- 239000000375 suspending agent Substances 0.000 description 1
- 239000003765 sweetening agent Substances 0.000 description 1
- 208000024891 symptom Diseases 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
- 239000006188 syrup Substances 0.000 description 1
- 235000020357 syrup Nutrition 0.000 description 1
- 239000003826 tablet Substances 0.000 description 1
- 239000013076 target substance Substances 0.000 description 1
- 230000008685 targeting Effects 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- UXAWXZDXVOYLII-YUMQZZPRSA-N tert-butyl (1s,4s)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate Chemical compound C1[C@@H]2N(C(=O)OC(C)(C)C)C[C@H]1NC2 UXAWXZDXVOYLII-YUMQZZPRSA-N 0.000 description 1
- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 125000003831 tetrazolyl group Chemical group 0.000 description 1
- 125000001113 thiadiazolyl group Chemical group 0.000 description 1
- 239000002562 thickening agent Substances 0.000 description 1
- VXUYXOFXAQZZMF-UHFFFAOYSA-N titanium(IV) isopropoxide Chemical compound CC(C)O[Ti](OC(C)C)(OC(C)C)OC(C)C VXUYXOFXAQZZMF-UHFFFAOYSA-N 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 125000004306 triazinyl group Chemical group 0.000 description 1
- TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
- 125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 description 1
- 125000004205 trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- NQPHMXWPDCSHTE-UHFFFAOYSA-N trifluoromethanesulfonyl azide Chemical compound FC(F)(F)S(=O)(=O)N=[N+]=[N-] NQPHMXWPDCSHTE-UHFFFAOYSA-N 0.000 description 1
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 1
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 description 1
- OJZNYUDKNVNEMV-UHFFFAOYSA-M trimethylstannanylium;hydroxide Chemical compound C[Sn](C)(C)O OJZNYUDKNVNEMV-UHFFFAOYSA-M 0.000 description 1
- JBWKIWSBJXDJDT-UHFFFAOYSA-N triphenylmethyl chloride Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(Cl)C1=CC=CC=C1 JBWKIWSBJXDJDT-UHFFFAOYSA-N 0.000 description 1
- 229910052722 tritium Inorganic materials 0.000 description 1
- 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000004614 tumor growth Effects 0.000 description 1
- 208000029729 tumor suppressor gene on chromosome 11 Diseases 0.000 description 1
- 230000005760 tumorsuppression Effects 0.000 description 1
- OUYCCCASQSFEME-UHFFFAOYSA-N tyrosine Natural products OC(=O)C(N)CC1=CC=C(O)C=C1 OUYCCCASQSFEME-UHFFFAOYSA-N 0.000 description 1
- 210000003462 vein Anatomy 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/08—Bridged systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/517—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D519/00—Heterocyclic compounds containing more than one system of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring system not provided for in groups C07D453/00 or C07D455/00
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- General Health & Medical Sciences (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- Medicinal Chemistry (AREA)
- Public Health (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Epidemiology (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP2021021656 | 2021-02-15 | ||
| PCT/JP2022/005582 WO2022173032A1 (fr) | 2021-02-15 | 2022-02-14 | Composé quinazoline pour induire la dégradation de la protéine kras de mutation g12d |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| IL305077A true IL305077A (en) | 2023-10-01 |
Family
ID=82838828
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| IL305077A IL305077A (en) | 2021-02-15 | 2022-02-14 | A quinazoline compound for inducing degradation of the G12D mutant cras protein |
Country Status (19)
| Country | Link |
|---|---|
| US (1) | US20240182483A1 (fr) |
| EP (1) | EP4293024A1 (fr) |
| JP (2) | JP7169729B1 (fr) |
| KR (1) | KR20230145361A (fr) |
| CN (1) | CN116848120A (fr) |
| AR (1) | AR124870A1 (fr) |
| AU (1) | AU2022221145A1 (fr) |
| BR (1) | BR112023015067A2 (fr) |
| CA (1) | CA3211051A1 (fr) |
| CL (1) | CL2023002383A1 (fr) |
| CO (1) | CO2023010710A2 (fr) |
| CR (1) | CR20230404A (fr) |
| DO (1) | DOP2023000161A (fr) |
| EC (1) | ECSP23067156A (fr) |
| IL (1) | IL305077A (fr) |
| MX (1) | MX2023009521A (fr) |
| PE (1) | PE20240235A1 (fr) |
| TW (1) | TW202245751A (fr) |
| WO (1) | WO2022173032A1 (fr) |
Families Citing this family (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO2023119677A1 (fr) * | 2021-12-24 | 2023-06-29 | Astellas Pharma Inc. | Composition pharmaceutique comprenant un composé quinazoline |
| AR128761A1 (es) * | 2022-03-11 | 2024-06-12 | Astellas Pharma Inc | Compuesto heterocíclico para inducir la degradación de la proteína kras mutante en g12d |
| WO2024029613A1 (fr) * | 2022-08-05 | 2024-02-08 | アステラス製薬株式会社 | Composé hétérocyclique destiné à induire la dégradation de la protéine kras portant une mutation |
| TW202413346A (zh) * | 2022-08-09 | 2024-04-01 | 日商安斯泰來製藥股份有限公司 | 用於誘導g12v突變kras蛋白之分解之雜環化合物 |
| TW202412790A (zh) * | 2022-08-09 | 2024-04-01 | 日商安斯泰來製藥股份有限公司 | 用於抑制及/或誘導分解kras蛋白之雜環化合物 |
| TW202412809A (zh) * | 2022-08-12 | 2024-04-01 | 日商安斯泰來製藥股份有限公司 | 包含標靶療法的抗癌組合 |
| WO2024033538A1 (fr) * | 2022-08-12 | 2024-02-15 | Astellas Pharma Inc. | Association d'agents anticancéreux comprenant un composé bifonctionnel ayant une activité inhibitrice de kras mutant g12d |
| WO2024034123A1 (fr) * | 2022-08-12 | 2024-02-15 | アステラス製薬株式会社 | Composition médicinale contenant un composé hétérocyclique |
| CN115873018B (zh) * | 2022-11-18 | 2024-03-15 | 中国药科大学 | 苯并嘧啶和苯并三嗪类造血祖细胞激酶1降解剂及其应用 |
Family Cites Families (12)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP2802608A4 (fr) * | 2012-01-12 | 2015-08-05 | Univ Yale | Composés et procédés pour la dégradation améliorée de protéines cibles et d'autres polypeptides par une e3 ubiquitine ligase |
| KR20210132233A (ko) | 2014-04-14 | 2021-11-03 | 아비나스 오퍼레이션스, 인코포레이티드 | 단백질분해의 이미드-기초된 조절인자 및 연관된 이용 방법 |
| WO2016049568A1 (fr) | 2014-09-25 | 2016-03-31 | Araxes Pharma Llc | Méthodes et compositions permettant l'inhibition de la ras |
| WO2016049565A1 (fr) | 2014-09-25 | 2016-03-31 | Araxes Pharma Llc | Compositions et procédés pour inhiber la ras |
| WO2017172979A1 (fr) * | 2016-03-30 | 2017-10-05 | Araxes Pharma Llc | Composés quinazoline substitués et procédés d'utilisation |
| US10646488B2 (en) | 2016-07-13 | 2020-05-12 | Araxes Pharma Llc | Conjugates of cereblon binding compounds and G12C mutant KRAS, HRAS or NRAS protein modulating compounds and methods of use thereof |
| JOP20190186A1 (ar) * | 2017-02-02 | 2019-08-01 | Astellas Pharma Inc | مركب كينازولين |
| JP2021521112A (ja) | 2018-04-04 | 2021-08-26 | アルビナス・オペレーションズ・インコーポレイテッドＡｒｖｉｎａｓ Ｏｐｅｒａｔｉｏｎｓ， Ｉｎｃ． | タンパク質分解の調節因子および関連する使用方法 |
| EP3823613A4 (fr) | 2018-07-20 | 2022-05-11 | Dana Farber Cancer Institute, Inc. | Agents de dégradation ciblant des protéines par l'intermédiaire de keap1 |
| WO2021041671A1 (fr) | 2019-08-29 | 2021-03-04 | Mirati Therapeutics, Inc. | Inhibiteurs de kras g12d |
| WO2021051034A1 (fr) | 2019-09-13 | 2021-03-18 | Biotheryx, Inc. | Agents de dégradation de la protéine ras, compositions pharmaceutiques de ceux-ci et leurs applications thérapeutiques |
| WO2021106231A1 (fr) | 2019-11-29 | 2021-06-03 | Taiho Pharmaceutical Co., Ltd. | Composé ayant une activité inhibitrice contre la mutation kras g12d |
-
2022
- 2022-02-14 AR ARP220100290A patent/AR124870A1/es unknown
- 2022-02-14 IL IL305077A patent/IL305077A/en unknown
- 2022-02-14 WO PCT/JP2022/005582 patent/WO2022173032A1/fr active Application Filing
- 2022-02-14 PE PE2023002366A patent/PE20240235A1/es unknown
- 2022-02-14 MX MX2023009521A patent/MX2023009521A/es unknown
- 2022-02-14 TW TW111105240A patent/TW202245751A/zh unknown
- 2022-02-14 EP EP22752854.4A patent/EP4293024A1/fr active Pending
- 2022-02-14 CR CR20230404A patent/CR20230404A/es unknown
- 2022-02-14 JP JP2022542202A patent/JP7169729B1/ja active Active
- 2022-02-14 CN CN202280014815.8A patent/CN116848120A/zh active Pending
- 2022-02-14 AU AU2022221145A patent/AU2022221145A1/en active Pending
- 2022-02-14 US US18/268,001 patent/US20240182483A1/en active Pending
- 2022-02-14 KR KR1020237027669A patent/KR20230145361A/ko unknown
- 2022-02-14 BR BR112023015067A patent/BR112023015067A2/pt unknown
- 2022-02-14 CA CA3211051A patent/CA3211051A1/fr active Pending
- 2022-10-27 JP JP2022172197A patent/JP2022191505A/ja active Pending
-
2023
- 2023-08-11 CL CL2023002383A patent/CL2023002383A1/es unknown
- 2023-08-15 DO DO2023000161A patent/DOP2023000161A/es unknown
- 2023-08-16 CO CONC2023/0010710A patent/CO2023010710A2/es unknown
- 2023-09-05 EC ECSENADI202367156A patent/ECSP23067156A/es unknown
Also Published As
| Publication number | Publication date |
|---|---|
| KR20230145361A (ko) | 2023-10-17 |
| JP2022191505A (ja) | 2022-12-27 |
| CN116848120A (zh) | 2023-10-03 |
| AR124870A1 (es) | 2023-05-17 |
| PE20240235A1 (es) | 2024-02-16 |
| DOP2023000161A (es) | 2023-09-29 |
| JPWO2022173032A1 (fr) | 2022-08-18 |
| TW202245751A (zh) | 2022-12-01 |
| MX2023009521A (es) | 2023-08-24 |
| JP7169729B1 (ja) | 2022-11-11 |
| ECSP23067156A (es) | 2023-10-31 |
| CA3211051A1 (fr) | 2022-08-18 |
| CO2023010710A2 (es) | 2023-09-18 |
| BR112023015067A2 (pt) | 2023-10-03 |
| CR20230404A (es) | 2023-09-21 |
| AU2022221145A1 (en) | 2023-09-21 |
| EP4293024A1 (fr) | 2023-12-20 |
| WO2022173032A1 (fr) | 2022-08-18 |
| CL2023002383A1 (es) | 2024-01-19 |
| US20240182483A1 (en) | 2024-06-06 |
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